Senescence in Monocytes Facilitates Dengue Virus Infection by Increasing Infectivity

• Published in: Frontiers in cellular and infection microbiology Vol. 10; p. 375
• Main Authors: Hsieh, Tzu-Han, Tsai, Tsung-Ting, Chen, Chia-Ling, Shen, Ting-Jing, Jhan, Ming-Kai, Tseng, Po-Chun, Lin, Chiou-Feng
• Format: Journal Article
• Language: English
• Published: Switzerland Frontiers Media S.A 28.07.2020
• Subjects: Cellular and Infection Microbiology; DC-SIGN; dengue virus; IL-10; monocytes; senescence; senescence; monocytes; DC-SIGN; IL-10; dengue virus
• ISSN: 2235-2988; 2235-2988
• DOI: 10.3389/fcimb.2020.00375

Aging and chronic condition increase the incidence of dengue virus (DENV) infection, generally through a mechanism involving immunosenescence; however, the alternative effects of cellular senescence, which alters cell susceptibility to viral infection, remain unknown. Human monocytic THP-1 cells (ATCC TIB-202) treated with D-galactose to induce cellular senescence were susceptible to DENV infection. These senescent cells showed increased viral entry/binding, gene/protein expression, and dsRNA replication. The use of a replicon system showed that pharmacologically induced senescence did not enhance the effects on viral protein translation. By examining viral receptor expression, we found increased expression of CD209 (DC-SIGN) in the senescent cells. Interleukin (IL)-10 was aberrantly produced at high levels by the senescent cells, and the expression of the DENV receptor DC-SIGN was increased in these senescent cells, partially via IL-10-mediated regulation of the JAK2-STAT3 signaling pathway. The results demonstrate that a senescent phenotype facilitates DENV infection, probably by increasing DC-SIGN expression.